Malaria is caused by blood protozoa of the genus Plasmodium. The four species of Plasmodium that infect humans are Plasmodium vivax, P. malariae, P. ovale and P. falciparum, the last one is responsible for producing severe complications and cerebral malaria, which can cause the patient to lapse into a coma and ultimately leads to death. In many parts of the world, strains of P. falciparum have emerged which are resistant to chloroquine, mefloquine, halofantrine, quinine and sulfadoxin+pyrimethamine combination, and sulfa methopyrazine+pyrimethamine combinations the trusted drugs of choice for control of malaria. Like-wise P. vivax infections resistant to chloroquine are emerging in different countries. More than 270 million people suffer from the disease, and 1.2-1.7 million deaths occur yearly. Mortality is more among children under 5 years of age who are specially sensitive because of their lack of immunity to the disease (Ziffer H; Highet RJ and Klayman DL; Artemisinin an endoperoxide antimalarial from A. annua. Progress in the chemistry of organic natural product: Herz W (Ed).Springer-Wien New York, 1997, P. 121-214).
Severe complicated malaria is a life--threatening condition and comatose cerebral malaria cases need emergency parental therapy. Severe P. falciparum infections are common in both rural and urban areas and the management of these cases becomes difficult because of emerging problems of drug resistant infections. The comatose cases generally do not survive more than 72 hrs and therefore, require urgent antimalarial drug therapy. The suppository preparations of a variety of antimalarials can be effectively used as emergency treatment in rural areas as well as primary health care centres and these can be easily administered even by unskilled health workers in remote areas. Several reports have been published which support the observation that rectal suppository preparations of artemisinin have powerful effect in reducing the falciparum parasitaemia in critically sick and severe cases including cerebral complications (Vinh et al. (1997), Trans Roy Soc. Trop. Med. Hyg. 91, 465-467; Li et al 1985, J Trad. Chinese Med. 5, 159-161).
The endoperoxides are a promising class of antimalarial drugs which may meet the dual challenges posed by drug resistant parasites and the rapid progression of severe malarial illness and complications which can prove fatal unless emergency treatment is instituted. Artemisinin, is a sesquiterpene lactone containing an endoperoxide bridge (C--O--O--C) and is unique among the antimalarial drugs. Dihydroartemisinin (DHA) is the reduced lactol derivative of artemisinin and the semisynthetic derivatives (artemether, arteether, artesunate and artelinate) are ethers or esters of the lactol. In general, the endoperoxides present in all these derivatives, have several advantages over existing antimalarial drugs. These derivatives show little or no cross-resistance to existing antimalarials. The endoperoxides are fast-acting and clear the periphera blood of parasites more rapidly than other available drugs and finally resistance to the endoperoxides has not yet developed, despite widespread clinical trials. (White N.J., 1994, Artemisinin Current Status:Trans R. Soc. Trop Med Hyg. (88 Suppl), 53-54). The attractive feature of the drugs (arteether, artemether) is the lack of systemic neurotoxicity at the clinically prescribed doses (Looaresuwan, S. et al. 1997 Acta. Tropica. 67, 197-205).